Studies are proposed to test the hypothesis that factors released from injured peripheral nerves undergoing demyelination are involved in promoting the localized, injury-induced cell proliferation which results in tissue repair and wound healing. This hypothesis, which is supported by earlier studies of nerve degeneration, is especially reasonable in light of the recent finding that the mitogenic polypeptic termed fibroblast growth factor (FGF) is derived proteolytically from myelin basic protein (MBP), a principal protein constituent of myelin. Investigations will focus on the amputated urodele amphibian limb because this system permits quantitative manipulation of the nervous supply to the injured tissue in vivo and because cellular responses of such limbs have been well characterized in previous studies on limb regeneration. A series of experiments in which the proliferative response elicited by amputation is measured will test (1) the effects of the state of nerve degeneration at the time of amputation, (2) the effects of the presence of antiserum to MBP or to FGF, and (3) the effects in vitro and in vivo of exogenously applied FGF. Results will be assayed by standard biochemical methods for the measurement of DNA and protein synthesis and by autoradiographic procedures for the determination of DNA labeling indices in the responding tissues. The objective of the research is not only to characterize more fully the cellular response of vertebrate tissues to injury, but also to elucidate possible physiological roles of FGF. Anticipated results will be relevant to reparative processes in mammals and to certain aspects of several demyelinating diseases.